Int J Clin Exp Pathol 2013;6(5):973-977

www.ijcep.com /ISSN:1936-2625/IJCEP1302030

Case Report
Good response of malignant pleural effusion from
carcinoma of unknown primary site to the
anti-tuberculosis therapy: a case report
Qihua Gu, Chengping Hu, Jingjing Qu
Department of respiratory medicine, Xiangya Hospital affiliated to Central South University, Changsha City, Hunan,
410008, P.R. China
Received February 21, 2013; Accepted March 19, 2013; Epub April 15, 2013; Published April 30, 2013
Abstract: Malignant pleural effusion in patients with cancers or malignant pleural mesothelioma may often appear
at the late stage of disease and significantly affect the patients life quality and survival. However, there is still no
very effective treatment to control malignant pleural effusion. Here we report that malignant pleural effusion in one
patient was completely relieved for 15 months by the anti-tuberculosis therapy. Case presentation: A 54-year-old
female patient complained of cough, dyspnea, chest pain, night sweat and light fever in the afternoon. Computed
tomography (CT) of the chest revealed bilateral pleural effusion. But no tumor was found in the lung, pleura and
in other sites. Blood test revealed serum carcinoembryonic antigen (CEA) level at 300 ng/mL. One week after
we tried anti-tuberculosis combined therapy with isoniazid, pyrazinamide, rifapentine and ethambutol. The pleural
effusion in patient was eliminated, along with decreasing CEA. But the CEA increased gradually again when the
anti-tuberculosis treatment was forced to discontinuation. Sixteen months after anti-tuberculosis treatment, the
symptoms of cough and breathing difficulty relapsed. Chest CT revealed left pleural effusion, pleural thickness and
pericardium nodules. Thoracoscopy and biopsy were conducted. The pleural nodules specimen was pathologically
diagnosed as squamous cell carcinoma. Conclusion We reported a rare case of successfully treating malignant
pleural effusion caused by squamous cell carcinoma of unknown primary site with the anti-tuberculosis combined.
This report provides useful evidences for that the anti-tubercular agents may have potential anticancer activity in
some carcinomas.
Keywords: Malignant pleural effusion, carcinoembryonic antigen (CEA), anti-tuberculosis therapy

Introduction
According to the original diseases, pleural effusions can be classified into benign pleural effusion and malignant pleural effusion. Malignant
pleural effusion is encountered at the advanced
stage of disease progression and often associates with poor prognosis [1]. Malignant pleural
effusion in patients with metastatic cancers or
malignant pleural mesothelioma, may often
appear at the late stage of disease and significantly reduce the patients life quality and survival [2, 3]. The incidence of benign pleural
effusions is twice as malignant effusions and
has diverse causes and manifestations [4].
There are several common benign pleural effusions that caused by tuberculosis, pneumonia,
congestive heart failure, hypoproteinemia, etc.

Clinical outcome of benign pleural effusion

depends greatly on its original disease. For this
reason, once a patient is first diagnosed with
the pleural effusion, it is necessary to determine if the patient has transudates or exudates
[5]. Etiological diagnosis should be performed
to achieve optimal treatment. However, etiological diagnosis is very difficult in some circumstances, such as few cases of malignant pleural effusion. It has been reported that
metastatic cancer of unknown primary site
accounts for approximately 3% of all malignant
neoplasms [6]. In the present report, we report
a case of malignant pleural effusion caused by
squamous cell carcinoma of unknown primary
site. More importantly, malignant pleural effusion was completely relieved for 15 months by
fortunate treatment with the anti-tuberculosis

Anti-tuberculosis therapy for malignant pleural effusion

Figure 1. Computed tomography of the patient. A. Initial examination. Chest CT revealed bilateral pleural effusion,
but no tumor was found in the lung and pleura; B. One week after anti-tuberculosis therapy, the patients pleural
effusion was eliminated; C. Eleven months later, there was still no pleural effusion; D. Sixteen months later, Chest
CT revealed left pleural effusion, pleural thickness and pericardium nodules.

combined therapy of isoniazid, pyrazinamide,

rifapentine and ethambutol.
Case presentation
A 54-year-old female patient was hospitalized
in June 2010 because of cough and dyspnea.
The patient had the symptoms of intermittent
cough, breathing difficulty after activities and
chest pain for 10 days. She also had clinical
symptoms of light fever (body temperature rose
at 37.5C) in the afternoon, fatigue, and night
sweat. Physical examination revealed dull
sound on percussion and decreased breath
sounds in the low lung areas by auscultation.
Computed tomography (CT) revealed bilateral
pleural effusion (Figure 1A). But no tumor was
found in the lung, pleura and in other sites. We
conducted thoracic puncture and identified
bloody pleural effusion. No carcinoma cells
were found in the pleural effusion. The serum
carcinoembryonic antigen (CEA) level was 300
ng/mL in blood test. The patient also had a
positive result (greater than 10 mm, ++) in purified protein derivative (PPD) skin test. The
patient was primarily diagnosed as tuberculous
pleurisy according to clinical manifestations
and auxiliary examination, but metastatic carcinoma remained to be excluded. We planed to
conduct thoracoscopy after pretreatment of

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isoniazid, pyrazinamide, rifapentine and ethambutol. One week after treatment, the pleural
effusion was eliminated (Figure 1B), along with
reduced CEA (131.9 ng/mL). Two months after
anti-tuberculosis treatment, pyrazinamide was
subtractive. Four months after treatment, the
anti-tuberculosis treatment was forced to discontinuation because of skin pruritus, erythema and rash. The CEA subsequently increased
gradually again. Clinical manifestations and
auxiliary examinations in the follow-up periods
are shown in Table 1. The patient felt light chest
pain in August 2011. The symptoms of cough
and breathing difficulties relapsed in September
2011. Chest CT revealed left pleural effusion
(Figure 1D), pleural thickness and pericardium
nodules. Single photon emission computed
tomography (SPECT) revealed that multiple
bone metastatic lesions (Figure 2A). But no primary tumor was found by positron emission
tomography-computed tomography (PET-CT).
Thoracoscopy and biopsy were conducted. The
pleural nodules specimen was identified as
squamous cell carcinoma by pathological diagnosis (Figure 2B-D).
Discussion
We experienced a rare case of patient who had
malignant pleural effusion from carcinoma of

Int J Clin Exp Pathol 2013;6(5):973-977

Anti-tuberculosis therapy for malignant pleural effusion

Table 1. The patients records of symptoms, chest CT and CEA
Time
Onset
1 week
1 month
4 months
6 months
9 months
12 months
15 months
16 months

Clinical symptoms
cough, dyspnea, chest pain, light fever,
night sweat.
symptoms disappeare
no symptoms
pruritus, erythemas, rash.
no symptoms
no symptoms
no symptoms
light chest pain
chest pain, cough, breathing difficulties

Chest CT
bilateral pleural effusion

CEA
300 (ng/mL)

pleural effusion disappeared

no pleural effusion
no pleural effusion
no pleural effusion
no pleural effusion
no pleural effusion
no pleural effusion
left pleural effusion pleural nodules

131 ng/mL
30 ng/mL
13 ng/mL
23 ng/mL
50 ng/mL
72 ng/mL
536 ng/mL
712 ng/mL

Figure 2. Evidences of final diagnosis in the patient.

A. Single photon emission computed tomography revealed multiple bone metastatic lesions; B. Posterior
part of costal pleura, multiple nodules was observed
under thoracoscopy; C. Thoracoscopy and biopsy.
Nodular lesions of parietal pleura were collected
through thoracoscopy; D. Image of HE staining. Histopathological analysis of the pleural nodules specimen
revealed squamous cell carcinoma.

unknown primary site and got a remarkable

clinical remission by treatment of anti-tuberculosis. The patient was finally diagnosed as metastatic squamous cell carcinoma by thoracoscopy and biopsy. When the patient was treated
with the anti-tuberculosis therapy, such symptoms as chest pain, fever and night sweat were
quickly relieved, the pleural effusion disappeared, and the serum level of CEA was
reduced. During the follow-up period, clinical
symptoms of the patient, pleural effusion and
serum CEA were changed consistently. CEA is a
tumor marker for many carcinomas. Moreover,

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the tumor marker index from serum and lavage

CEA levels might be useful for predicting the
prognosis of non-small cell lung cancer patients
[7]. For this patient, the primary tumor site
remained unknown in the final diagnosis. It has
been reported that lung cancer and mesothelioma are common causes of malignant pleural
effusion. Moreover, elevated CEA level can be
found in small-sized peripheral-lung squamous
cell carcinomas [8]. Tuberculous pleurisy was
excluded, so we suspect that malignant pleural
effusion in this patient was most possibly
caused by small-sized peripheral-lung squa-

Int J Clin Exp Pathol 2013;6(5):973-977

Anti-tuberculosis therapy for malignant pleural effusion

mous cell carcinoma. Metastatic pleural effusion from lung cancer has a particularly poor
prognosis [9]. Therefore, it deserves much
attention to the effective treatment on this
patient who achieved 15 months of complete
clinical remission.

Declaration

During the whole process, no anticancer chemotherapy and radiotherapy were given to this
patient. So the anti-tuberculosis combined
therapy of isoniazid, pyrazinamide, rifapentine
and ethambutol is the only explanation for the
elimination of pleural effusion and reduction of
serum CEA level. So the susceptivity to antituberculosis chemotherapy is not always helpful to confirm that the pleural effusion is definitely caused by tuberculous pleurisy. To date,
little is known about whether the anti-tuberculosis medicines have effect on human carcinoma. However, ethambutol was reported to have
a considerable antitumour activity against
Lewis lung carcinoma [10]. Rifapentine is a
cyclopentyl rifamycin, which kills tuberculosis
bacteria by inhibiting bacterial RNA polymerase.
Also, a study demonstrated the presence of
dose-dependent pyrazinamide-mediated quantitative and qualitative changes in rats [11].
Based on these literatures, it is possible that
some antitubercular drugs may have potential
anticancer activity in some carcinomas, such
as small-sized peripheral-lung squamous cell
carcinoma with high CEA level. Therefore, further experiments and the understanding of
such antitubercular agents as isoniazid, pyrazinamide, rifapentine and ethambutol are
required for the better treatment in malignant
pleural effusion.

CT, Computed tomography; CEA, Carcinoembryonic antigen; PPD, purified protein derivative; PET-CT, positron emission tomographycomputed tomography; SPECT, Single photon
emission computed tomography.

Conclusion

[5]

We reported a rare case of the patient who had

malignant pleural effusion caused by squamous cell carcinoma of unknown primary site
and high level of CEA. The malignant pleural
effusion was relieved for 15 months after treatment with the anti-tuberculosis combined therapy of isoniazid, pyrazinamide, rifapentine and
ethambutol. Therefore, some anti-tubercular
drugs may have potential anticancer activity in
some carcinomas.

[6]

Consent
Written informed consent was obtained from
the patient for publication of this case report.
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The authors declare that they have no competing interests.

Abbreviations

Address correspondence to: Dr. Qihua Gu,

Department of Respiratory Medicine, Xiangya
Hospital affiliated to Central South University,
Changsha City, Hunan, 410008, P.R. China. E-mail:
guqihua@yahoo.com.cn

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Int J Clin Exp Pathol 2013;6(5):973-977